Sina Nazari

Sina Nazari

A Neuroscience Invention to Celebrate

So far, I have written about business and personal development. At the moment though, I cannot resist the urge to write about neuroscience because of a new and exciting innovation in research techniques I want everyone to be aware of. On June 1, 2017, the journal Cell published an article from Ed Boyden’s lab at MIT, which I will explain in simple terms and discuss its implications for neuroscientists.

Let’s begin with some background. All the processing power of the brain comes from nerve cells called neurons. Neurons carry messages by means of electrical activity and transmit these messages to nearby neurons by releasing chemicals called neurotransmitters. The tools that alter neuronal activity in an animal brain’s specific region or specific brain circuit – either electrical or chemical signals – can be used to research the role of different parts of the brain and even to treat neurological and psychiatric disorders that stem from abnormal brain rhythms. In research, we can deduce the functionalities of brain regions by stimulating these regions and observing the behaviors that are generated or inhibited. As for health applications, brain stimulation has proven to be particularly useful in treating Parkinson’s disease, which is caused by abnormal neurotransmitter release and electrical signaling of cells in deep-lying nuclei of the brain.

Currently, the strongest and most commonly used method of altering brain activity is deep brain stimulation (DBS). In DBS, electrodes are inserted through the skull and are implanted in exact brain regions where they deliver an electrical current, and effectively correct their activity levels. DBS is widely used for treating Parkinson’s disease, depression, and PTSD. Especially for Parkinson’s disease, DBS fixes the abnormal brain signals and reduces the patient’s tremors with immediate effect. However, DBS is an invasive surgery procedure that is costly and requires trained neurosurgeons to perform. Even then, as with every other neurosurgical procedure, the patient has a risk of brain infection and stroke.

Many scientists believed that DBS would be replaced with optogenetic surgical techniques. Optogenetics is localized and precise, just like DBS. But it is also selective with respect to the neurotransmitter it mimics. An optogenetics surgery would involve inserting a fiber optic cable into the brain – which is thinner than an electrode – and illuminate light in the brain. This might sound a little irrational considering nature does not allow light into our brains, but this light is of a particular wavelength and is illuminated onto neurons which have been genetically “prepared” to be activated by light of this wavelength instead of (or in addition to by) neurotransmitters. To summarize, optogenetics is also invasive and precise but it is selective in terms of activating cells which typically respond to a certain neurotransmitter.

There are also non-invasive brain stimulation techniques like direct-current stimulation or transcranial magnetic stimulation. These techniques offer limited access to the brain. Non-invasive stimulation of deeper brain areas requires a current that would pass through and activate the surface brain regions (e.g. cortex) located between deep areas and the skull, reducing the specificity of this technique and causing side effects.

Enter Ed Boyden’s invention called “Temporal Interference DBS, or TI DBS”. This method allows neuroscientists to simulate specifically deep parts of the brain without surgery or any invasive procedure. It takes advantage of two facts: 1) Neurons typically respond to low-frequency electrical currents and ignore currents with frequencies greater than 1000Hz, and 2) two or more superimposed electric fields interfere with one another (a.k.a. physical phenomenon of temporal interference). Do you see where I’m going? Researchers used two electrodes on the surface of the brain to generate two or more high-frequency electrical currents of slightly different frequencies (e.g. 3000Hz vs 3010Hz). These currents interfere with one another all across the brain but are positioned such that they generate low-frequency signals at a precisely calculated part of the brain. The frequency difference (3010Hz – 3000Hz = 10Hz) is interpreted by the neurons in that part of the brain as low-frequency current, while the irregular interference of higher frequency signals is ignored by other parts of the brain. If the interference of low-frequency electrical activity is directed to deeper brain regions, then the brain surface receives high-frequency electrical fields which fail to activate neurons. Let me repeat the application of this technique: electrodes on the surface activate the targeted deep brain regions without activating surface neurons in the cortex! TI DBS is also easy to target: the location and size of the brain tissue stimulated can be determined by changing the frequency of currents and the location of the electrodes on the head.

This paper was not just theoretical. It describes highly practical experiments performed on mice: it confirmed that the application of high-frequency electrical fields “did not alter the number of dying neurons, did not increase brain tissue temperature beyond the normal range, nor did the mice experience seizures during or after the stimulations. However, like every new research method, it requires further exploration before it is adopted in many research labs. The following questions are yet to be answered:

Could the resolution of TI DBS be improved to target specific brain nuclei, in a way similar to DBS?

Is applying high-frequency current to the brain a safe practice?

Could we repeat the same experiments on the human brain, which is larger in size and covered behind a thicker skull?

Once these questions are answered, I hope we would have a technique for specific stimulation of deep brain areas that is non-invasive, inexpensive, and more accessible to the general public.